Correlative ultrastructural mapping of Lewy pathology reveals regional diversity in Parkinson’s and dementia with Lewy bodies - Summary - MDSpire

Correlative ultrastructural mapping of Lewy pathology reveals regional diversity in Parkinson’s and dementia with Lewy bodies

  • By

  • Notash Shafiei

  • Daria Proniakova

  • Marija Simjanoska

  • Anniken Mathea Rafnum Sjødal

  • Daniel Stähli

  • Lukas van den Heuvel

  • Marta Di Fabrizio

  • Eve Aaron

  • Sandor Kasas

  • Mathis Solal Krause

  • Mallory Wittwer

  • Julika Radecke

  • Henning Stahlberg

  • Wilma D. J. van de Berg

  • Amanda J. Lewis

  • July 8, 2026

  • 0 min

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Objective:

To investigate the regional diversity of alpha-synuclein (α-Syn) pathology in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) using correlative light and electron microscopy (CLEM).

Approach:
  • Study Design: Correlative light and electron microscopy (CLEM) was used to analyze α-Syn inclusions in various brain regions, including the entorhinal cortex (ENT), anterior cingulate cortex (ACC), hippocampus (CA2), and substantia nigra (SN) of DLB donors.
  • Sample Collection: Brain samples were obtained from four DLB, three PD, one Alzheimer’s, and two non-neurological control donors from the Netherlands Brain Bank.
  • Pathological Diagnosis: Immunohistochemistry was performed on brain sections to assess α-Syn pathology and other neurodegenerative markers.
Key Findings:
  • LB ultrastructure varies by brain region rather than by disease identity.
  • The ENT shows a spectrum of fibrillar densities, while the ACC has uniformly compact inclusions.
  • Regional and disease-specific differences in mitochondrial morphology were associated with α-Syn inclusions.
Interpretation:

Limitations:
  • The study's findings are based on a limited number of brain samples, which may affect the generalizability of the results.
  • Systematic regional comparisons of cortical LB pathology were previously lacking, limiting the understanding of disease mechanisms.
Conclusion:

This study extends previous ultrastructural descriptions of cortical Lewy pathology, providing new insights into its regional heterogeneity and molecular complexity in PD and DLB.

Original Source(s)

Correlative ultrastructural mapping of Lewy pathology reveals regional diversity in Parkinson’s and dementia with Lewy bodies

  • by Notash Shafiei, Daria Proniakova, Marija Simjanoska, Anniken Mathea Rafnum Sjødal, Daniel Stähli, Lukas van den Heuvel, Marta Di Fabrizio, Eve Aaron, Sandor Kasas, Mathis Solal Krause, Mallory Wittwer, Julika Radecke, Henning Stahlberg, Wilma D. J. van de Berg, Amanda J. Lewis

  • July 8, 2026

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